Design and characterisation of a minibeam collimator utilising Monte Carlo simulation and a clinical linear accelerator.

Objective.Spatially fractionated radiotherapy is showing promise as a treatment modality. Initial focus was on beams of photons at low energy produced from a synchrotron but more recently research has expanded to include applications in proton therapy. Interest in photon beams remains and this is the focus of this paperApproach.This study presents a 3D printed tungsten minibeam collimator intended to produce peak-to-valley dose ratios (PVDR) of between seven and ten with a 1 MV, bremsstrahlung generated, photon beam. The design of the collimator is motivated by a Monte Carlo study estimating the PVDR for different collimator designs at different energies. This collimator was characterised on a clinical linear accelerator (Elekta VersaHD) as well as an orthovoltage unit.Main results.The performance of the fabricated collimator was measured on Elekta VersaHD running in unflattened mode with a 6 MV beam. On the Elekta VersaHD units the PVDR was measured to be between approximately 1.5 and 2.0 at 3 cm deep. For measurements with the orthovoltage unit PVDRs of greater than 10 were observed at a depth of 4 cm.Significance.The results confirmed that the predictions from simulation could be reproduced on linear accelerators currently in clinical usage, producing PVDRs between 2-2.5. Using the model to predict PVDRs using 1 MV photon beams, the threshold considered to produce enhanced normal tissue dose tolerance (>7) was surpassed. This suggests the possibility of using such techniques with versions of existing Linac technology which have been modified to operate at low energy and high beam currents.

Peptide Binder to Glypican-3 as a Theranostic Agent for Hepatocellular Carcinoma.

Glypican-3 (GPC3) is a membrane-associated glycoprotein that is significantly upregulated in hepatocellular carcinomas (HCC) with minimal to no expression in normal tissues. The differential expression of GPC3 between tumor and normal tissues provides an opportunity for targeted radiopharmaceutical therapy to treat HCC, a leading cause of cancer-related deaths worldwide. Methods: DOTA-RYZ-GPC3 (RAYZ-8009) comprises a novel macrocyclic peptide binder to GPC3, a linker, and a chelator that can be complexed with different radioisotopes. The binding affinity was determined by surface plasma resonance and radioligand binding assays. Target-mediated cellular internalization was radiometrically measured at multiple time points. In vivo biodistribution, monotherapy, and combination treatments with 177Lu or 225Ac were performed on HCC xenografts. Results: RAYZ-8009 showed high binding affinity to GPC3 protein of human, mouse, canine, and cynomolgus monkey origins and no binding to other glypican family members. Potent cellular binding was confirmed in GPC3-positive HepG2 cells and was not affected by isotope switching. RAYZ-8009 achieved efficient internalization on binding to HepG2 cells. Biodistribution study of 177Lu-RAYZ-8009 showed sustained tumor uptake and fast renal clearance, with minimal or no uptake in other normal tissues. Tumor-specific uptake was also demonstrated in orthotopic HCC tumors, with no uptake in surrounding liver tissue. Therapeutically, significant and durable tumor regression and survival benefit were achieved with 177Lu- and 225Ac-labeled RAYZ-8009, as single agents and in combination with lenvatinib, in GPC3-positive HCC xenografts. Conclusion: Preclinical in vitro and in vivo data demonstrate the potential of RAYZ-8009 as a theranostic agent for the treatment of patients with GPC3-positive HCC.

Microbial Interspecies Associations in Fracture-Related Infection.

OBJECTIVES: Describe co-occurrence or clustering of microbial taxa in fracture-related infections to inform further exploration of infection-related interactions among them. DESIGN: Retrospective review. SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: Four hundred twenty-three patients requiring surgical intervention for deep surgical site infection between January 2006 and December 2015. INTERVENTION: None. MAIN OUTCOME MEASUREMENT: Connection between microbial taxa. RESULTS: Methicillin-resistant Staphylococcus aureus, methicillin-sensitive Staphylococcus aureus, and coagulase-negative Staphylococcus represented the majority of monomicrobial observations (71%). Gram-negative rods, gram-positive rods, and anaerobes presented more frequently in polymicrobial infections. Enterobacter, vancomycin-sensitive Enterococcus, and Pseudomonas are present in polymicrobial infections with the highest frequencies and represent the top 3 most important nodes within the microorganism framework, with the highest network centrality scores. CONCLUSIONS: The present study indicates that there are common microbial taxa (Enterobacter, Enterococcus, and Pseudomonas) that tend to co-occur with other microbes greater than 75% of the time. These commonly co-occurring microbes have demonstrated interactive relationships in other disease pathologies, suggesting that there may be similar important interactions in fracture-related infections. It is possible that these microbial communities play a role in the persistently high failure rate associated with management of infection after trauma. Future studies are needed to study the intermicrobial interactions that explain the frequency at which taxa co-occur. Understanding and potentially disrupting these intermicrobial relationships could inform improvements in the treatment of established infections and in the prevention of infection in high-risk patients. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Immediate Weight Bearing of Plated Both-Bone Forearm Fractures Using Eight Cortices Proximal and Distal to the Fracture in the Polytrauma Patient Is Safe.

INTRODUCTION: Rehabilitation of trauma patients is facilitated by surgical stabilization permitting weight bearing (WB) of the fractured extremity. Both-bone forearm fracture (BBFx) plate osteosynthesis is an accepted technique with high union and low complication rates; yet, postoperative WB protocols have not been adequately investigated. There exists concern for increased complications in plated BBFx fractures for patients prescribed immediate WB. We hypothesized that immediate WB of surgically treated BBFxs results in acceptable rates of complications. METHODS: Patients presenting to a Level-1 trauma center from 2007 to 2016 with a BBFx were identified retrospectively. Patients were skeletally mature, surgically treated with prescribed immediate WB protocol, and followed for 6 months or to fracture union. Collected data included demographics, fracture characteristics, associated injuries, and WB protocols for all extremities. Complications recorded included nonunion, hardware failure, and infection. Standard statistical comparisons were used to evaluate the risk of complication in polytrauma patients with modified lower extremity WB protocols (polytrauma group) and patients with no lower extremity WB restrictions (isolated group). RESULTS: Two hundred thirteen patients were included with 75 (35%) females and 138 (65%) males. Mean age was 40 years and mean follow-up was 46 weeks. There were 142 (67%) patients in the poly-trauma and 71 (33%) patients in the isolated groups. In the poly-trauma group 21 (10%) patients had bilateral lower extremity WB restrictions. There were 11 (6%) complications noted: 2 non-unions, 4 hardware failures, and 5 infections. Demographics did not vary between the two groups. There was no difference in complications in the isolated (5.7%) versus poly-trauma groups (5.0%) (P = 0.75). CONCLUSION: Immediate WB rehabilitation after BBFx plate osteosynthesis seems to be safe and associated with low nonunion and complication rates. Our results demonstrate that polytrauma patients using ambulatory aids for lower extremity injuries can immediately WB without increased risk compared with isolated BBFx patients.

Risk factors for treatment failure of fracture-related infections.

OBJECTIVE: Infection after fracture fixation is a potentially devastating outcome, and surgical management is frequently unsuccessful at clearing these infections. The purpose of this study is to determine if factors can be identified that are associated with treatment failure after operative management of a deep surgical site infection. METHODS: We retrospectively reviewed the billing system at a Level I trauma center between March 2006 and December 2015. We identified 451 patients treated for deep surgical site infection after fracture fixation at our center. A multivariate regression analysis was then performed to evaluate for factors associated with treatment failure. RESULTS: Mean follow-up was 2.3 years. One hundred fifty-six patients (35%) failed initial surgical management. Risk factors associated with treatment failure included initial culture results positive for polymicrobial organisms (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.0-2.4), removal of implants (OR, 1.9; 95% CI, 1.2-2.9), or Gustilo-Anderson IIIB/IIIC injury (OR, 2.0; 95% CI, 1.1-3.7). Increased body mass index and fulfilling the criteria to have a methicillin-resistant Staphylococcus aureus (MRSA) nasal swab screening showed a trend toward increased risk of failure. CONCLUSION: Treatment failure after deep surgical site infection was relatively common. Three distinct factors (polymicrobial infection, removal of implants, and IIIB/C fracture) were associated with failure to eradicate the infection in the first series of surgeries and antibiotics. These data might help guide clinicians as they counsel patients on the risk of treatment failure and might focus efforts to improve treatment toward patients at higher risk of treatment failure.

Twenty-Year Trends in Upper-Extremity Infections at a Single Urban Institution.

Purpose: Empiric antibiotic therapy for hand and upper-extremity infections aims to cover the most common causative organisms, which may change over time. The purpose of this study was to investigate the changes in the bacterial profile of upper-extremity infections over 2 decades at our institution. Methods: We performed a retrospective chart review of patients with upper-extremity infections treated at a single level 1 trauma center between 2001 and 2019. Patients older than 18 years who underwent surgical treatment for infection with operative cultures available were included. Patient demographics, comorbidities, and culture results were reviewed. Then, the distribution of organisms was analyzed for overall prevalence, and the profile of 2001-2010 was compared with that of 2010-2019 using a chi-square test. Results: A total of 237 patients (mean age, 43 years) met the criteria and were included in the study. Over the entire study period, the most isolated organism was Staphylococcus aureus, specifically the methicillin-resistant species. Methicillin-resistant S aureus remained the most common organism in both decades but declined over time from 47% in 2001-2010 to 27% in 2010-2019 (P < .05). There was a significant increase in the proportion of Streptococcus infections (from 6% to 17%; P < .05) and in polymicrobial infections (aerobic 8% to 28%, anaerobic 0% to 14%; P < .05). Enterobacter species were not isolated in 2001-2010 but comprised 13% of infections in the second decade (P < .05). Conclusions: Methicillin-resistant S aureus remains the most common organism isolated from upper-extremity infections, though there has been a decline over the last 20 years. Conversely, Streptococcal spp., Enterobacter spp. and polymicrobial infections have increased. This study demonstrates longitudinal shifts in the distribution of bacteria responsible for upper-extremity infections at our institution, and these trends can be considered when choosing future empiric therapy. Type of study/level of evidence: Prognostic IV.

Identifying the Safe Zone in Arthroscopic Anterior Elbow Capsulectomy: A Cadaveric Study.

The authors assessed the effects of forearm rotation on the proximity of the radial nerve and medial collateral ligament (MCL) to a proximal and a more distal arthroscopic anterior elbow capsulectomy. Arthroscopy was performed on 10 cadaveric specimens. Sutures were passed lateral to medial at the level of the radiocapitellar joint and at the proximal edge of the annular ligament. Dissection measured the distance to the radial nerve from the lateral starting point and to the MCL from the medial exit point in varying degrees of forearm rotation. The extent of brachialis muscle coverage of the radial nerve was documented. The distance from the starting point to the radial nerve increased in pronation at both levels. The medial extent of the capsulectomy remained a safe distance from the MCL. Brachialis muscle covered the radial nerve at both levels. Pronation increases the capsulectomy safe zone, including more distally, before encountering the radial nerve; the MCL is not at risk. [Orthopedics. 2020;43(5):e399-e403.].

ApoC-III Glycoforms Are Differentially Cleared by Hepatic TRL (Triglyceride-Rich Lipoprotein) Receptors.

OBJECTIVE: ApoC-III (apolipoprotein C-III) glycosylation can predict cardiovascular disease risk. Higher abundance of disialylated (apoC-III2) over monosialylated (apoC-III1) glycoforms is associated with lower plasma triglyceride levels. Yet, it remains unclear whether apoC-III glycosylation impacts TRL (triglyceride-rich lipoprotein) clearance and whether apoC-III antisense therapy (volanesorsen) affects distribution of apoC-III glycoforms. Approach and Results: To measure the abundance of human apoC-III glycoforms in plasma over time, human TRLs were injected into wild-type mice and mice lacking hepatic TRL clearance receptors, namely HSPGs (heparan sulfate proteoglycans) or both LDLR (low-density lipoprotein receptor) and LRP1 (LDLR-related protein 1). ApoC-III was more rapidly cleared in the absence of HSPG (t1/2=25.4 minutes) than in wild-type animals (t1/2=55.1 minutes). In contrast, deficiency of LDLR and LRP1 (t1/2=56.1 minutes) did not affect clearance of apoC-III. After injection, a significant increase in the relative abundance of apoC-III2 was observed in HSPG-deficient mice, whereas the opposite was observed in mice lacking LDLR and LRP1. In patients, abundance of plasma apoC-III glycoforms was assessed after placebo or volanesorsen administration. Volanesorsen treatment correlated with a statistically significant 1.4-fold increase in the relative abundance of apoC-III2 and a 15% decrease in that of apoC-III1. The decrease in relative apoC-III1 abundance was strongly correlated with decreased plasma triglyceride levels in patients. CONCLUSIONS: Our results indicate that HSPGs preferentially clear apoC-III2. In contrast, apoC-III1 is more effectively cleared by LDLR/LRP1. Clinically, the increase in the apoC-III2/apoC-III1 ratio on antisense lowering of apoC-III might reflect faster clearance of apoC-III1 because this metabolic shift associates with improved triglyceride levels.

Management of symptomatic os acromiale: a survey of the American shoulder and elbow surgeons.

BACKGROUND: The purpose of this paper was to survey members of the American Shoulder and Elbow Surgeons (ASES) to assess their opinion on management options, help highlight important clinical factors, and elucidate surgical preferences for the treatment of a symptomatic meso-os. METHODS: An online questionnaire was distributed to the active members of the ASES. The survey queried surgeon demographics and perioperative management preferences, and presented multiple clinical case scenarios of patients with a presumed symptomatic, unstable os acromiale. RESULTS: There were 116 ASES members who responded to the survey, and 26% (n = 30) who stated they do not operatively manage a symptomatic os. We identified two main clusters of respondents. Cluster 1 (n = 67) (as compared to cluster 2, n = 19) was comprised of surgeons with significantly more experience treating a symptomatic os acromiale (p < 0.05). These surgeons regarded gender, age, BMI, and hand dominance as important clinical factors when deciding when to proceed to surgery. Overall, arthroscopic management of the os was preferred, but those surgeons more experienced in treating os acromiale preferred open reduction and internal fixation (ORIF) in specific clinical cases. CONCLUSION: The survey findings reflect the current lack of consensus in the treatment of a unstable, symptomatic os acromiale. Overall, arthroscopic management was preferred by most surgeons, though ORIF was preferred in certain clinical scenarios by those more experienced with os acromiale. The overall preference for arthroscopy suggests a possible shift in the treatment paradigm for patients with symptomatic meso-acromions, but higher level studies are needed to substantiate these findings.

Low-Intensity Pulsed Ultrasound for Nonoperative Treatment of Scaphoid Nonunions: A Meta-Analysis.

Background: Scaphoid fractures progress to nonunion rates of up to 15% when non-displaced, and are even more frequent when the fracture is displaced. Standard treatment in these cases is surgery; however, individuals unable to undergo this operation, or for those who wish to try more conservative measures, there may be benefit from nonoperative options. Of these, low-intensity pulsed ultrasound (LIPUS) has been shown to improve fracture nonunion healing. The purpose of this study was to perform a comprehensive meta-analysis of relevant literature to determine success of the use of LIPUS for treatment of scaphoid nonunion. Methods: Utilizing PubMed, Embase, and Ovid databases, we performed a literature search using key terms for scaphoid nonunions. A total of 686 studies met initial search criteria. Studies reporting fewer than 5 cases, those not published in English, those not related to LIPUS nonoperative scaphoid nonunion treatment, and those without sufficient data were excluded. Five studies met these criteria, and statistical analysis was performed to determine overall union rates. Results: The use of LIPUS on 166 nonunions reported a mean healing index of 78.6%. The average time to union following LIPUS treatment was 4.2 months. Conclusions: While surgical intervention is still the standard, our results show that LIPUS may serve as a nonoperative alternative to scaphoid nonunion in certain cases. The results are encouraging in which these challenging fracture a nonunions can heal without further surgical intervention in the majority of patients.

Pannexin 1 Modulates Axonal Growth in Mouse Peripheral Nerves.

The pannexin family of channels consists of three members-pannexin-1 (Panx1), pannexin-2 (Panx2), and pannexin-3 (Panx3) that enable the exchange of metabolites and signaling molecules between intracellular and extracellular compartments. Pannexin-mediated release of intracellular ATP into the extracellular space has been tied to a number of cellular activities, primarily through the activity of type P2 purinergic receptors. Previous work indicates that the opening of Panx1 channels and activation of purinergic receptors by extracellular ATP may cause inflammation and apoptosis. In the CNS (central nervous system) and PNS (peripheral nervous system), coupled pannexin, and P2 functions have been linked to peripheral sensitization (pain) pathways. Purinergic pathways are also essential for other critical processes in the PNS, including myelination and neurite outgrowth. However, whether such pathways are pannexin-dependent remains to be determined. In this study, we use a Panx1 knockout mouse model and pharmacological inhibitors of the Panx1 and the ATP-mediated signaling pathway to fill gaps in our understanding of Panx1 localization in peripheral nerves, roles for Panx1 in axonal outgrowth and myelination, and neurite extension. Our data show that Panx1 is localized to axonal, myelin, and vascular compartments of the peripheral nerves. Knockout of Panx1 gene significantly increased axonal caliber in vivo and axonal growth rate in cultured dorsal root ganglia (DRG) neurons. Furthermore, genetic knockout of Panx1 or inhibition of components of purinergic signaling, by treatment with probenecid and apyrase, resulted in denser axonal outgrowth from cultured DRG explants compared to untreated wild-types. Our findings suggest that Panx1 regulates axonal growth in the peripheral nervous system.

Peculiar citric acid cycle of hydrothermal vent chemolithoautotroph Hydrogenovibrio crunogenus, and insights into carbon metabolism by obligate autotrophs.

The genome sequence of the obligate chemolithoautotroph Hydrogenovibrio crunogenus paradoxically predicts a complete oxidative citric acid cycle (CAC). This prediction was tested by multiple approaches including whole cell carbon assimilation to verify obligate autotrophy, phylogenetic analysis of CAC enzyme sequences and enzyme assays. Hydrogenovibrio crunogenus did not assimilate any of the organic compounds provided (acetate, succinate, glucose, yeast extract, tryptone). Enzyme activities confirmed that its CAC is mostly uncoupled from the NADH pool. 2-Oxoglutarate:ferredoxin oxidoreductase activity is absent, though pyruvate:ferredoxin oxidoreductase is present, indicating that sequence-based predictions of substrate for this oxidoreductase were incorrect, and that H. crunogenus may have an incomplete CAC. Though the H. crunogenus CAC genes encode uncommon enzymes, the taxonomic distribution of their top matches suggests that they were not horizontally acquired. Comparison of H. crunogenus CAC genes to those present in other 'Proteobacteria' reveals that H. crunogenus and other obligate autotrophs lack the functional redundancy for the steps of the CAC typical for facultative autotrophs and heterotrophs, providing another possible mechanism for obligate autotrophy.

Scapular neck length and implications for reverse total shoulder arthroplasty: An anatomic study of 442 cadaveric specimens.

PURPOSE: Reverse total shoulder arthroplasty (RTSA) may be used to treat a variety of pathologic shoulder conditions, but complications such as scapular notching continue raise concerns. Variable anatomy surrounding the glenoid may have implications for future RTSA design, but at present the anatomy of the scapular neck in the human population has not been clearly defined. MATERIALS AND METHODS: 442 human scapulae from the Hamann-Todd Osteological Collection were measured for scapular neck length (SNL) and scapular neck angle (SNA). SNL was defined as the distance from the most lateral portion of the infraglenoid tubercle to the most inferolateral portion of the glenoid fossa. The SNA was measured according to Gerber et al. previously. The mean, standard deviation and ranges for SNL and SNA were calculated and compared based on sex and race, and interobserver variability was calculated. RESULTS: The mean SNL was 1.06 cm ± 0.33 cm (0.37-2.43 cm). Males demonstrated a larger SNL (1.08 cm ± 0.33 cm) than females (1.01 cm ± 0.32 cm) (P < 0.12), and Caucasians (1.09 cm ± 0.33 cm) demonstrated a significantly larger SNL than African-Americans (1.00 cm ± 0.32) (P < 0.01). The mean SNA was 106.7° ± 11.0° (76.9-139.4°). No significant correlation was found between SNL and SNA (Pearson Correlation Coefficient = 0.018) (P < 0.702). CONCLUSION: Scapular neck length and SNA vary widely within the population but there appears to be a tendency towards increased SNL in males and Caucasians. CLINICAL RELEVANCE: The anatomy of the scapular neck may have significant implications for RTSA design, surgical planning, and reduction of associated complications.

Actin-myosin network influences morphological response of neuronal cells to altered osmolarity.

Acute osmotic fluctuations in the brain occur during a number of clinical conditions and can result in a variety of adverse neurological symptoms. Osmotic perturbation can cause changes in the volumes of intra- and extracellular fluid and, due to the rigidity of the skull, can alter intracranial pressure thus making it difficult to analyze purely osmotic effects in vivo. The present study aims to determine the effects of changes in osmolarity on SH-SY5Y human neuroblastoma cells in vitro, and the role of the actin-myosin network in regulating this response. Cells were exposed to hyper- or hypoosmotic media and morphological and cytoskeletal responses were recorded. Hyperosmotic shock resulted in a drop in cell body volume and planar area, a persisting shape deformation, and increases in cellular translocation. Hypoosmotic shock did not significantly alter planar area, but caused a transient increase in cell body volume and an increase in cellular translocation via the development of small protrusions rich in actin. Disruption of the actin-myosin network with latrunculin and blebbistatin resulted in changes to volume and shape regulation, and a decrease in cellular translocation. In both osmotic perturbations, no apparent disruptions to cytoskeletal integrity were observed by light microscopy. Overall, because osmotically induced changes persisted even after volume regulation occurred, it is possible that osmotic stress may play a larger role in neurological dysfunction than currently believed.

New engineering treatment of bovine pericardium confers outstanding resistance to calcification in mitral and pulmonary implantations in a juvenile sheep model.

OBJECTIVE: To conduct a test of noninferiority for CardioCel (Admedus, Brisbane, Australia), a chemically engineered bovine pericardium over autologous pericardium treated intraoperatively with glutaraldehyde in a chronic juvenile sheep model of pulmonary valve (PV) and mitral valve (MV) reconstruction. METHODS: We replaced the posterior leaflet of the MV and of 1 PV cusp with patches in ewes aged 10 months. There were 2 groups: CardioCel (n = 6) and control (n = 4). All valves were competent. Echocardiography was performed before euthanasia. The collected data were function, macroscopy, histology, and calcium contents. The primary end points were thickening and calcium content. RESULTS: All animals survived until sacrifice after 7 months. The valves had normal echo. The macroscopic aspect of the valves was excellent. Examination of the slides for both groups revealed a continuous endothelium on both sides of the patch and a layer of new collagen developed on both sides between patch and endothelium and interstitial cells and smooth muscle cell in these layers. The patch had not thickened but the 2 layers of new collagen for the PV showed a median thickening of 37% in the CardioCel group and 111% in the control group (P = .01), and for the MV a thickening of 108% and 251%, respectively, was seen (P = .01). The median calcium content in the PV was 0.24 µg/mg (range, 0.19-0.30) in the CardioCel group versus 0.34 µg/mg (range, 0.24-0.62) in controls (P = .20). In the MV it was 0.46 µg/mg (range, 0.30-1.0) in the CardioCel group and 0.47 µg/mg (range, 0.29-1.9) in controls (P = 1.0). CONCLUSIONS: In this growing lamb model the CardioCel patch allowed accurate valve repair at both systemic and pulmonary pressure. The mechanical properties of CardioCel after 7 months were preserved with a more controlled healing than the treated autologous pericardium and without calcification.

Impact of levosimendan on brain injury patterns in a lamb model of infant cardiopulmonary bypass.

BACKGROUND: The effects of levosimendan (Levo) on injury patterns in the immature brain following cardiopulmonary bypass (CPB) are unknown. METHODS: Eighteen 3- to 4-wk-old anesthetized lambs, instrumented with vascular catheters and aortic and right carotid artery flow probes, were allocated to non-CPB, CPB, or CPB+Levo groups (each n = 6). After 120 min CPB with 90 min aortic cross-clamp, CPB animals received dopamine, and CPB+Levo animals both dopamine and Levo, for 4 h. All lambs then underwent brain magnetic resonance imaging, followed by postmortem brain perfusion fixation for immunohistochemical studies. RESULTS: In CPB lambs, aortic (P < 0.05) and carotid artery (P < 0.01) blood flows fell by 29 and 30%, respectively, between 2 and 4 h after cross-clamp removal but were unchanged in the CPB+Levo group. No brain injury was detectable with magnetic resonance imaging in either CPB or CPB+Levo lambs. However, on immunohistochemical analysis, white matter astrocyte density of both groups was higher than in non-CPB lambs (P < 0.05), while white matter microglial density was higher (P < 0.05), but markers of cortical oxidative stress were less prevalent in CPB+Levo than CPB lambs. CONCLUSION: While Levo prevented early postoperative falls in cardiac output and carotid artery blood flow in a lamb model of infant CPB, this was associated with heterogeneous neuroglial activation and manifestation of markers of oxidative stress.

Mechanisms of a reduced cardiac output and the effects of milrinone and levosimendan in a model of infant cardiopulmonary bypass.

OBJECTIVES: A low cardiac output state is an important cause of morbidity after pediatric cardiopulmonary bypass. The objectives of our study were to define the early precipitants of the reduced cardiac output and to investigate the effects on these of milrinone and levosimendan in a model of pediatric cardiopulmonary bypass. DESIGN: Experimental study. SETTING: : Research laboratory at a university-affiliated, tertiary pediatric center. SUBJECTS: Eighteen piglets. INTERVENTIONS: Piglets, instrumented with systemic, pulmonary arterial, and coronary sinus catheters, pulmonary and circumflex arterial flow probes, and a left ventricular conductance-micromanometer-tipped catheter, underwent cardiopulmonary bypass with aortic cross-clamp and cardioplegic arrest. At 120 mins, they were assigned to control, milrinone, or levosimendan groups and studied for a further 120 mins. MEASUREMENTS AND MAIN RESULTS: In controls, between 120 and 240 mins, cardiac output decreased by 15%. Systemic vascular resistance was unchanged, but pulmonary vascular resistance increased by 19%. Systemic arterial elastance increased by 17%, indicating increased afterload. End-systolic elastance was unchanged, and coronary sinus oxygen tension decreased by 4.0 +/- 1.7 mm Hg. In animals receiving milrinone cardiac output was preserved, and in animals receiving levosimendan cardiac output increased by 14%. Both drugs prevented an increase in arterial elastance and pulmonary vascular resistance after cardiopulmonary bypass. Systemic vascular resistance decreased by 31% after levosimendan, and end-systolic elastance increased by 48%, indicating improved contractility. Both agents prevented a decrease in coronary sinus oxygen tension. CONCLUSIONS: Increased afterload, which is not matched by an equivalent elevation in contractility, contributes to the reduced cardiac output early after pediatric cardiopulmonary bypass in this model. This increase is prevented by milrinone and levosimendan. Both agents exert additional beneficial effects on pulmonary vascular resistance and myocardial oxygen balance, although levosimendan has greater inotropic properties.

Smooth muscle neoplasm presenting as intrapericardial myxoma.

This report describes the echocardiographic appearance of an intrapericardial mass and pericardial effusion in an otherwise healthy patient. The tumor was a globular mass attached to the left atrium by a stalk, suggestive of a myxoma. The mass was successfully excised and the patient had an uneventful recovery. Histology revealed a smooth muscle tumor with extensive adipocytic differentiation and numerous small blood vessels. This study represents the first echocardiographic description of a smooth muscle tumor presenting as an extracardiac myxoma.